ABSTRACT This is a competing renewal application to continue funding the Texas Node (TxN) of the NIDA Clinical Trials Network (CTN). During the previous funding period the TxN, based at the University of Texas Southwestern Medical Center in Dallas, made substantial contributions to CTN research, the scientific literature, and dissemination and training activities. TxN study sites were top performers across the 8 CTN trials implemented. TxN scientists developed and led three studies: the first large study to evaluate exercise as a novel intervention for stimulant use, a genetics study, and a study using electronic health records (EHRs). Outstanding contributions to the field were made, with 38 publications and 57 presentations. Over 300 addiction treatment providers were trained in several evidence-based practices via annual workshops hosted by the TxN. Scientists mentored junior investigators, resulting in funded grants and publications. Changes made to increase efficiency, decrease expenditures, and continually improve performance during the previous funding period have uniquely prepared the TxN to perform superbly during the next period. This renewal application capitalizes on over 20 years of experience of the PI, Madhukar H. Trivedi, MD, and the experiences of other key investigators through its emphasis on primary care networks, large systems of care, and use of EHRs to positively impact substance use. Building on the TxN?s solid foundation of collaborating with specialty addiction community treatment programs, additional partnerships have been secured with healthcare networks that provide access to varied patient populations throughout Texas and the US. These networks are excited to work with the TxN and the CTN. Partners include one of the largest adolescent outpatient primary care networks in the US, one of the largest safety net hospital systems in the US, and the American Academy of Family Physicians National Research Network. Other important collaborating groups include the national VA Substance Use Disorder ? Quality Enhancement Research Initiative, Patient Centered Outcomes Research Institute?s Greater Plains Collaborative, and the National Center for Advancing Translational Sciences Accrual for Clinical Trials. The TxN research agenda, which focuses on early identification and intervention, is consistent with the CTN?s priorities, addresses clinical needs identified by node partners, and capitalizes on expertise in the TxN. The TxN aims to answer questions of critical importance to the field by utilizing innovative interventions as well as EHR- and other technology-based methods, at the point of primary care, to significantly improve the care of persons who misuse substances.